Detoxification of certain highly lipophilic endogenous substrates and noxious foreign compounds, such as pollutants, require a multistep process. The thrust of research efforts in the Section of Developmental Pharmacology has been to develop experimental models for studying drug metabolism in cell culture and in a colony of inbred strains of mice, with special focus on the initial steps (phase I) in detoxification. Previously, research in this Section has established that certain mono-oxygenases (phase I enzymes) are regulated at a few genetic loci, and that expression of enzyme induction is dominant or codominant in response to aromatic hydrocarbon treatment. The aim of this research is to attempt to understand the impact of secondary reactions (phase II) on the detoxification process. Whether mono-oxygenase activity (phase I enzyme) is genetically associated with UDP glucuronyl transferase (phase II enzyme) and the regulatory mechanisms underlying induction of phase II enzymes will be the major directions of this project.